Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Nature Genetics

Volumn 47, Issue 12, 2015, Pages 1449-1456

  Paternoster, Lavinia ^a,b   Standl, Marie ^c   Waage, Johannes ^d   Baurecht, Hansjörg ^e   Hotze, Melanie ^e   Strachan, David P ^f   Curtin, John A ^g   Bønnelykke, Klaus ^d   Tian, Chao ^h   Takahashi, Atsushi ⁱ   Esparza Gordillo, Jorge ^j,k   Alves, Alexessander Couto ^l   Thyssen, Jacob P ^d   Den Dekker, Herman T ^m   Ferreira, Manuel A ⁿ   Altmaier, Elisabeth ^c   Sleiman, Patrick M A ^o,p   Xiao, Feng Li ^q   Gonzalez, Juan R ^r,s,t   Marenholz, Ingo ^j,k   Kalb, Birgit ^j,k   Pino Yanes, Maria ^u,v,w   Xu, Cheng Jian ^x   Carstensen, Lisbeth ^y   Groen Blokhuis, Maria M ^z   Venturini, Cristina ^aa   Pennell, Craig E ^ab   Barton, Sheila J ^ac   Levin, Albert M ^ad   Curjuric, Ivan ^ae,af   Bustamante, Mariona ^r,s,t,ag   Kreiner Møller, Eskil ^d   Lockett, Gabrielle A ^ah   Bacelis, Jonas ^ai   Bunyavanich, Supinda ^aj   Myers, Rachel A ^ak   Matanovic, Anja ^j,k   Kumar, Ashish ^ae,af,al,am   Tung, Joyce Y ^h   Hirota, Tomomitsu ⁱ   Kubo, Michiaki ⁱ   McArdle, Wendy L ^b   Henderson, A John ^b   Kemp, John P ^a,b,an   Zheng, Jie ^a,b   Smith, George Davey ^a,b   Rüschendorf, Franz ^j   Bauerfeind, Anja ^j   Lee Kirsch, Min Ae ^ao   Arnold, Andreas ^ap   Homuth, Georg ^aq   Schmidt, Carsten O ^ap   Mangold, Elisabeth ^ar   Cichon, Sven ^af,ar,as,at   Keil, Thomas ^k,au   Rodríguez, Elke ^e   Peters, Annette ^c,av   Franke, Andre ^aw   Lieb, Wolfgang ^aw   Novak, Natalija ^ax   Fölster Holst, Regina ^e   Horikoshi, Momoko ^am   Pekkanen, Juha ^ay,az   Sebert, Sylvain ^ba,bb   Husemoen, Lise L ^bc   Grarup, Niels ^bd   De Jongste, Johan C ^m   Rivadeneira, Fernando ^m   Hofman, Albert ^m   Jaddoe, Vincent W V ^m   Pasmans, Suzanne G M A ^m   Elbert, Niels J ^m   Uitterlinden, André G ^m   Marks, Guy B ^be   Thompson, Philip J ^bf,bg   Matheson, Melanie C ^bh   Robertson, Colin F ^bi   Ried, Janina S ^c   Li, Jin ^o   Zuo, Xian Bo ^q   Zheng, Xiao Dong ^q   Yin, Xian Yong ^q   Sun, Liang Dan ^q   McAleer, Maeve A ^bj,bk   O'Regan, Grainne M ^bk   Fahy, Caoimhe M R ^bl   Campbell, Linda E ^bm   Macek, Milan ^bn   Kurek, Michael ^bo   Hu, Donglei ^u   Eng, Celeste ^u   Postma, Dirkje S ^x   Feenstra, Bjarke ^y   Geller, Frank ^y   Hottenga, Jouke Jan ^z   Middeldorp, Christel M ^z   Hysi, Pirro ^aa   Bataille, Veronique ^aa   Spector, Tim ^aa   Tiesler, Carla M T ^c,bp   Thiering, Elisabeth ^c,bp   Pahukasahasram, Badri ^ad   Yang, James J ^bq   Imboden, Medea ^ae,af   Huntsman, Scott ^u   Vilor Tejedor, Natàlia ^r,s,t   Relton, Caroline L ^a,br   Myhre, Ronny ^bs   Nystad, Wenche ^bs   Custovic, Adnan ^g   Weiss, Scott T ^bt   Meyers, Deborah A ^bu   Söderhäll, Cilla ^al   Melén, Erik ^al,bv   Ober, Carole ^ak   Raby, Benjamin A ^bt   Simpson, Angela ^g   Jacobsson, Bo ^ai,bs   Holloway, John W ^ah   Bisgaard, Hans ^d   Sunyer, Jordi ^r,s,t,bw   Probst Hensch, Nicole M ^ae,af   Williams, L Keoki ^ad   Godfrey, Keith M ^ac,bx   Wang, Carol A ^ab   Boomsma, Dorret I ^z,by   Melbye, Mads ^y,bz,ca   Koppelman, Gerard H ^cb   Jarvis, Deborah ^cc,cd   McLean, W H Irwin ^bm   Irvine, Alan D ^bj,bk,bl   Zhang, Xue Jun ^q   Hakonarson, Hakon ^o,p   Gieger, Christian ^c   Burchard, Esteban G ^u,ce   Martin, Nicholas G ⁿ   Duijts, Liesbeth ^m   Linneberg, Allan ^bc,bz,cf   Jarvelin, Marjo Riitta ^ba,bb,cd,cg   Nöthen, Markus M ^ar   Lau, Susanne ^k   Hübner, Norbert ^j   Lee, Young Ae ^j,k   Tamari, Mayumi ⁱ   Hinds, David A ^h   Glass, Daniel ^aa   Brown, Sara J ^bm,ch   Heinrich, Joachim ^c   Evans, David M ^a,b,an   Weidinger, Stephan ^e   more..

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^f ST GEORGE S HOSPITAL   (United Kingdom)

^g UNIVERSITY OF MANCHESTER   (United Kingdom)

^h Institute of Physical and Chemical Research ^*  (United States)

ⁱ Institute of Physical and Chemical Research   (Japan)

^j MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^k CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^l IMPERIAL COLLEGE LONDON   (United Kingdom)

^m ERASMUS MEDICAL CENTER   (Netherlands)

ⁿ QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^o CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^p UNIVERSITY OF PENNSYLVANIA   (United States)

^q ANHUI MEDICAL UNIVERSITY   (China)

^r CENTRE FOR RESEARCH IN ENVIRONMENTAL EPIDEMIOLOGY CREAL   (Spain)

^s UNIVERSITAT POMPEU FABRA   (Spain)

^t CIBER EPIDEMIOLOGÍA Y SALUD PÚBLICA CIBERESP   (Spain)

^u UNIVERSITY OF CALIFORNIA   (United States)

^v INSTITUTO DE SALUD CARLOS III   (Spain)

^w HOSPITAL UNIVERSITARIO NUESTRA SEÑORA DE CANDELARIA   (Spain)

^x UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^y STATENS SERUM INSTITUT   (Denmark)

^z VU UNIVERSITY AMSTERDAM   (Netherlands)

^aa KING'S COLLEGE LONDON   (United Kingdom)

^ab UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^ac UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^ad HENRY FORD HEALTH SYSTEM   (United States)

^ae SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^af UNIVERSITY OF BASEL   (Switzerland)

^ag CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^ah UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^ai SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^aj MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^ak UNIVERSITY OF CHICAGO   (United States)

^al KAROLINSKA INSTITUTE   (Sweden)

^am UNIVERSITY OF OXFORD   (United Kingdom)

^an UNIVERSITY OF QUEENSLAND   (Australia)

^ao DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^ap UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^aq UNIVERSITY OF GREIFSWALD   (Germany)

^ar UNIVERSITY OF BONN   (Germany)

^as UNIVERSITY HOSPITAL BASEL   (Switzerland)

^at FORSCHUNGSZENTRUM JÜLICH   (Germany)

^au UNIVERSITY OF WÜRZBURG   (Germany)

^av DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^aw UNIVERSITY OF KIEL   (Germany)

^ax UNIVERSITY HOSPITAL BONN   (Germany)

^ay NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^az UNIVERSITY OF HELSINKI   (Finland)

^ba UNIVERSITY OF OULU   (Finland)

^bb UNIVERSITY OF OULU   (Finland)

^bc Research for Prevention and Health   (Denmark)

^bd University of Copenhagen   (Denmark)

^be UNIVERSITY OF SYDNEY   (Australia)

^bf PATHWEST LABORATORY MEDICINE   (Australia)

^bg UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^bh UNIVERSITY OF MELBOURNE   (Australia)

^bi MURDOCH CHILDREN'S RESEARCH INSTITUTE   (Australia)

^bj National Children's Research Centre   (Ireland)

^bk OUR LADY S CHILDREN S HOSPITAL   (Ireland)

^bl TRINITY COLLEGE DUBLIN   (Ireland)

^bm UNIVERSITY OF DUNDEE   (United Kingdom)

^bn UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^bo POMERANIAN MEDICAL UNIVERSITY   (Poland)

^bp LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^bq UNIVERSITY OF MICHIGAN   (United States)

^br NEWCASTLE UNIVERSITY   (United Kingdom)

^bs NORWEGIAN INSTITUTE OF PUBLIC HEALTH   (Norway)

^bt HARVARD MEDICAL SCHOOL   (United States)

^bu WAKE FOREST SCHOOL OF MEDICINE   (United States)

^bv SACHS CHILDREN S HOSPITAL   (Sweden)

^bw HOSPITAL DEL MAR   (Spain)

^bx UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^by UNIVERSITY OF AMSTERDAM   (Netherlands)

^bz UNIVERSITY OF COPENHAGEN   (Denmark)

^ca STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^cb UNIVERSITY OF GRONINGEN   (Netherlands)

^cc NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^cd PUBLIC HEALTH ENGLAND   (United Kingdom)

^ce UNIVERSITY OF CALIFORNIA   (United States)

^cf International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health   (Denmark)

^cg OULU UNIVERSITY HOSPITAL   (Finland)

^ch UNIVERSITY OF DUNDEE   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

FILAGGRIN; IMMUNOGLOBULIN E; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; LCE3E PROTEIN; MRPS21 PROTEIN; PATTERN RECOGNITION RECEPTOR; PPP2R3C PROTEIN; PROTEIN; STAT3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 3; SYNAPTOJANIN; TRANSCRIPTION FACTOR SP1; TRANSCRIPTION FACTOR SP3; TRANSCRIPTION FACTOR SP4; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 3; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; GENETIC MARKER;

AFRICAN; ALLERGY; ANCESTRY GROUP; ANKYLOSING SPONDYLITIS; ARTICLE; ASTHMA; ATOPIC DERMATITIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; BINDING SITE; CELL DIFFERENTIATION; CHINESE; CONTROLLED STUDY; DISEASE SEVERITY; EFFECT SIZE; ENZYME ACTIVITY; ENZYME REPRESSION; ETS1 GENE; EUROPEAN; GENE; GENE DELETION; GENE EXPRESSION; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE REPLICATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC IDENTIFICATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC TRAIT; GENETIC VARIABILITY; GENOME; HERPES SIMPLEX VIRUS; HISPANIC; HOST RESISTANCE; HUMAN; IMMUNOGLOBULIN BLOOD LEVEL; INFLAMMATORY BOWEL DISEASE; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; JAPANESE (PEOPLE); LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; MALASSEZIA; META ANALYSIS; MOLECULAR PHYLOGENY; MULTIPLE SCLEROSIS; NONHUMAN; ONSET AGE; PATHOGENESIS; PHENOTYPE; POLLEN ALLERGY; PRIORITY JOURNAL; PSORIASIS; QUANTITATIVE TRAIT LOCUS; RECURRENT INFECTION; RHEUMATOID ARTHRITIS; SELF REPORT; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; STAPHYLOCOCCUS AUREUS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; ZBTB10 GENE; CASE CONTROL STUDY; CYTOLOGY; ETHNIC GROUP; ETHNOLOGY; GENETIC MARKER; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; IMMUNOLOGY; METABOLISM; PATHOLOGY; RISK FACTOR;

CASE-CONTROL STUDIES; DERMATITIS, ATOPIC; ETHNIC GROUPS; GENETIC LOCI; GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; IMMUNITY, INNATE; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS; T-LYMPHOCYTES;

EID: 84949087646     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3424     Document Type: Article

References (69)

1. Weidinger, S. & Novak, N. Atopic dermatitis. Lancet doi:10.1016/S0140-6736(15)00149-X (13 September 2015).
2. Bataille, V., Lens, M. & Spector, T.D. The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data. J. Eur. Acad. Dermatol. Venereol. 26, 1067-1073 (2012).
3. Irvine, A.D., McLean, W.H. & Leung, D.Y. Filaggrin mutations associated with skin and allergic diseases. N. Engl. J. Med. 365, 1315-1327 (2011).
4. Palmer, C.N.A. et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 38, 441-446 (2006).
5. Rodríguez, E. et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J. Allergy Clin. Immunol. 123, 1361-1370 (2009).
6. Weidinger, S. et al. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum. Mol. Genet. 22, 4841-4856 (2013).
7. Ellinghaus, D. et al. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat. Genet. 45, 808-812 (2013).
8. Hirota, T. et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat. Genet. 44, 1222-1226 (2012).
9. Paternoster, L. et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat. Genet. 44, 187-192 (2012).
10. Sun, L.-D. et al. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat. Genet. 43, 690-694 (2011).
11. Esparza-Gordillo, J. et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat. Genet. 41, 596-601 (2009).
12. Esparza-Gordillo, J. et al. A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis. J. Allergy Clin. Immunol. 132, 371-377 (2013).
13. Agarwala, V., Flannick, J., Sunyaev, S., Go, T.D.C. & Altshuler, D. Evaluating empirical bounds on complex disease genetic architecture. Nat. Genet. 45, 1418-1427 (2013).
14. Hinds, D.A. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat. Genet. 45, 907-911 (2013).
15. Ferreira, M.A.R. et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378, 1006-1014 (2011).
16. Himes, B.E. et al. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am. J. Hum. Genet. 84, 581-593 (2009).
17. Noguchi, E. et al. Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations. PLoS Genet. 7, e1002170 (2011).
18. Moffatt, M.F. et al. A large-scale, consortium-based genomewide association study of asthma. N. Engl. J. Med. 363, 1211-1221 (2010).
19. Sleiman, P.M. et al. Variants of DENND1B associated with asthma in children. N. Engl. J. Med. 362, 36-44 (2010).
20. Hirota, T. et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat. Genet. 43, 893-896 (2011).
21. Bønnelykke, K. et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat. Genet. 45, 902-906 (2013).
22. Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119-124 (2012).
23. Tsoi, L.C. et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44, 1341-1348 (2012).
24. International Genetics of Ankylosing Spondylitis Consortium. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat. Genet. 45, 730-738 (2013).
25. International Multiple Sclerosis Genetics Consortium. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476, 214-219 (2011).
26. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376-381 (2014).
27. Bradfield, J.P. et al. A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genet. 7, e1002293 (2011).
28. Niwa, Y., Sumi, H. & Akamatsu, H. An association between ulcerative colitis and atopic dermatitis, diseases of impaired superficial barriers. J. Invest. Dermatol. 123, 999-1000 (2004).
29. Jakobsen, C., Paerregaard, A., Munkholm, P. & Wewer, V. Environmental factors and risk of developing paediatric inflammatory bowel disease-a population based study 2007-2009. J. Crohns Colitis 7, 79-88 (2013).
30. Baron, S. et al. Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study. Gut 54, 357-363 (2005).
31. Henseler, T. & Christophers, E. Disease concomitance in psoriasis. J. Am. Acad. Dermatol. 32, 982-986 (1995).
32. Baurecht, H. et al. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am. J. Hum. Genet. 96, 104-120 (2015).
33. Segrè, A.V. et al. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).
34. Wellcome Trust Case Control Consortium. Bayesian refinement of association signals for 14 loci in 3 common diseases. Nat. Genet. 44, 1294-1301 (2012).
35. Grundberg, E. et al. Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat. Genet. 44, 1084-1089 (2012).
36. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74 (2012).
37. Bernstein, B.E. et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28, 1045-1048 (2010).
38. Malissen, B., Tamoutounour, S. & Henri, S. The origins and functions of dendritic cells and macrophages in the skin. Nat. Rev. Immunol. 14, 417-428 (2014).
39. de Jong, M.A. & Geijtenbeek, T.B. Langerhans cells in innate defense against pathogens. Trends Immunol. 31, 452-459 (2010).
40. Baker, B.S. The role of microorganisms in atopic dermatitis. Clin. Exp. Immunol. 144, 1-9 (2006).
41. Tang, T.S., Bieber, T. & Williams, H.C. Does "autoreactivity" play a role in atopic dermatitis? J. Allergy Clin. Immunol. 129, 1209-1215 (2012).
42. Kitabatake, M. et al. Transgenic overexpression of G5PR that is normally augmented in centrocytes impairs the enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice. J. Immunol. 189, 1193-1201 (2012).
43. Lundström, W., Fewkes, N.M. & Mackall, C.L. IL-7 in human health and disease. Semin. Immunol. 24, 218-224 (2012).
44. Gregory, S.G. et al. Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39, 1083-1091 (2007).
45. Lundmark, F. et al. Variation in interleukin 7 receptor α chain (IL7R) influences risk of multiple sclerosis. Nat. Genet. 39, 1108-1113 (2007).
46. Lundström, W. et al. Soluble IL7Rα potentiates IL-7 bioactivity and promotes autoimmunity. Proc. Natl. Acad. Sci. USA 110, E1761-E1770 (2013).
47. Uehira, M., Matsuda, H., Nakamura, A. & Nishimoto, H. Immunologic abnormalities exhibited in IL-7 transgenic mice with dermatitis. J. Invest. Dermatol. 110, 740-745 (1998).
48. Steward-Tharp, S.M. et al. A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3. Blood 123, 2978-2987 (2014).
49. H17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452, 773-776 (2008).
50. Lupski, J.R., Belmont, J.W., Boerwinkle, E. & Gibbs, R.A. Clan genomics and the complex architecture of human disease. Cell 147, 32-43 (2011).
51. Blair, D.R. et al. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk. Cell 155, 70-80 (2013).
52. Mertens-Talcott, S.U., Chintharlapalli, S., Li, X. & Safe, S. The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 67, 11001-11011 (2007).
53. Ferreira, M.A. et al. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. J. Allergy Clin. Immunol. 133, 1564-1571 (2014).
54. Stritesky, G.L., Jameson, S.C. & Hogquist, K.A. Selection of self-reactive T cells in the thymus. Annu. Rev. Immunol. 30, 95-114 (2012).
55. Moisan, J., Grenningloh, R., Bettelli, E., Oukka, M. & Ho, I.C. Ets-1 is a negative regulator of Th17 differentiation. J. Exp. Med. 204, 2825-2835 (2007).
56. Nagarajan, P. et al. Ets1 blocks terminal differentiation of keratinocytes and induces expression of matrix metalloproteases and innate immune mediators. J. Cell Sci. 123, 3566-3575 (2010).
57. Beck, L.A. et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N. Engl. J. Med. 371, 130-139 (2014).
58. Granada, M. et al. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J. Allergy Clin. Immunol. 129, 840-845 (2012).
59. Ramasamy, A. et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J. Allergy Clin. Immunol. 128, 996-1005 (2011).
60. Morris, A.P. Transethnic meta-analysis of genomewide association studies. Genet. Epidemiol. 35, 809-822 (2011).
61. Wang, X. et al. Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies. Hum. Mol. Genet. 22, 2303-2311 (2013).
62. Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369-375 (2012).
63. Nyholt, D.R. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Hum. Genet. 74, 765-769 (2004).
64. Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001-D1006 (2014).
65. Cole, C. et al. Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis. J. Allergy Clin. Immunol. 134, 82-91 (2014).
66. Tintle, S. et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J. Allergy Clin. Immunol. 128, 583-593 (2011).
67. Giambartolomei, C. et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 10, e1004383 (2014).
68. Maurano, M.T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190-1195 (2012).
69. So, H.C., Li, M. & Sham, P.C. Uncovering the total heritability explained by all true susceptibility variants in a genome-wide association study. Genet. Epidemiol. 35, 447-456 (2011).